Implantable graft to close a fistula

ABSTRACT

An implantable graft, which may be inserted into a fistula tract to occlude the primary opening of the fistula, is provided. The graft may have a curved, generally conical shape with a trumpet-like head end that continuously tapers to a smaller tail end. The graft may be an integral unit made of a single material, such as a heterograft material. Methods of closing single and multiple fistulae are also provided.

RELATED APPLICATIONS

The present patent application is a continuation of U.S. patentapplication Ser. No. 11/807,801, filed May 30, 2007 (now U.S. Pat. No.8,764,791) which is a division of U.S. patent application Ser. No.11/040,996, filed Jan. 21, 2005 which claims the benefit of the filingdate under 35 U.S.C. §119(e) of Provisional U.S. Patent Application Ser.No. 60/538,365, filed Jan. 21, 2004. The contents of the priorapplications are hereby incorporated by reference.

FIELD OF THE INVENTION

A graft for occluding a fistula is provided. The graft may be pulled,tail first, into the fistula to completely occlude the fistula, therebyavoiding a surgical fistulotomy and its attendant complications.

BACKGROUND OF THE INVENTION

Fistulae occur commonly in man. Such fistulae may be congenital or maybe caused by infection, inflammatory bowel disease (Crohn's disease),irradiation, trauma, childbirth, or surgery, for example.

Some fistulae occur between the vagina and the bladder (vesico-vaginalfistulae) or between the vagina and the urethra (urethro-vaginalfistulae). These fistulae may be caused by trauma during childbirth.Traditional surgery for these types of fistulae is complex and not verysuccessful.

Other fistulae include, but are not limited to, tracheo-esophagealfistulae, gastro-cutaneous fistulae, and anorectal fistulae. Forexample, anorectal fistulae may occur between the anorectum and vagina(recto-vaginal fistulae), between the anorectum and bladder(recto-vesical fistulae), between the anorectum and urethra(recto-urethral fistulae), or between the anorectum and prostate(recto-prostatic fistulae). Anorectal fistulae may result from infectionin the anal glands, which are located around the circumference of thedistal anal canal forming an anatomic landmark known as the dentate line1, shown in FIGS. 1 and 2. Approximately 20-39 such glands are found inman. Infection in an anal gland may result in an abscess, which thentracks through or around the sphincter muscles into the perianal region,where it drains either spontaneously or surgically. The resulting tractis known as a fistula. The inner opening of the fistula, usually locatedat the dentate line, is known as the primary opening 2. The outer(external) opening, located in the perianal skin, is known as thesecondary opening 3.

FIGS. 1 and 2 show examples of the various paths that an anorectalfistula may take. These paths vary in complexity. Fistulae that take astraight line path from the primary opening 2 to the secondary opening 3are known as simple fistulae 4. Fistula that contain multiple tractsramifying from the primary opening 2 and have multiple secondaryopenings 3 are known as complex fistulae 5.

The anatomic path that an anorectal fistula takes is classifiedaccording to its relationship to the anal sphincter muscles 6, 7. Theanal sphincter includes two concentric bands of muscle—the inner, orinternal, sphincter 6 and the outer, or external, anal sphincter 7.Fistulae which pass between the two concentric anal sphincters are knownas inter-sphincteric fistulae 8. Those which pass through both internal6 and external 7 sphincters are known as trans-sphincteric fistulae 9,and those which pass above both sphincters are called supra-sphinctericfistulae 10. Fistulae resulting from Crohn's disease usually ignorethese anatomic paths, and are known as extra-anatomic fistulae.

Many complex fistulae contain multiple tracts, some blind-ending 11 andothers leading to multiple secondary openings 3. One of the most commonand complex types of fistulae are known as horseshoe fistulae 12, asillustrated in FIG. 2. In this instance, the infection starts in theanal gland (the primary opening 2) and two fistulae passcircumferentially around the anal canal, forming a characteristichorseshoe configuration 12.

Surgical treatment of fistulae traditionally involves passing a fistulaprobe through the tract, in a blind manner, using only tactile sensationand experience to guide the probe. Having passed the probe through thefistula tract, the overlying tissue is surgically divided. This is knownas a surgical fistulotomy. Because a variable amount of sphincter muscleis divided during the procedure, fistulotomy may result in impairedsphincter control or even incontinence.

Alternatively, the fistula tract may be surgically drained by insertinga narrow diameter rubber drain, known as a seton, through the tract.After the seton is passed through the fistula tract, it may be tied as aloop around the contained tissue and left for several weeks or months.This procedure is usually performed to drain infection from the area andto mature the fistula tract prior to a definitive closure or sealingprocedure.

More recently, methods have evolved to inject sclerosant or sealant(collagen or fibrin glue) into the tract of the fistula. Such sealantsare described in Rhee, U.S. Pat. No. 5,752,974, for example. The maindrawback with these methods is that the glues have a liquid consistencyand tend to run out of the fistula tract once the patient becomesambulatory. In addition, failure rates of these methods are high (up to86% failure). See Buchanan et al., Efficacy of Fibrin Sealant in theManagement of Complex Anal Fistula, DIS COLON AND RECTUM Vol. 46, No. 9,46:1167-1174 (September 2003). Usually, multiple injections of glue arerequired to close the fistula. In some instances, closure of a fistulausing a sealant may be performed as a two-stage procedure, comprising afirst-stage seton placement, followed by injection of the fibrin glueseveral weeks later. This procedure reduces residual infection andallows the fistula tract to “mature” prior to injecting a sealant.Injecting sealant or sclerosant into an unprepared or infected fistulaas a one-stage procedure may cause a flare-up of the infection and evenfurther abscess formation. Alternative methods and instruments, such ascoring-out instruments (See, e.g., U.S. Pat. Nos. 5,628,762 and5,643,305), simply make the fistula wider and more difficult to close.

An additional means of closing the primary opening is by surgicallycreating a flap of skin, which is drawn across the opening and suturedin place. This procedure (the endo-anal flap procedure) closes theprimary opening, but is technically difficult to perform, is painful forthe patient, and is associated with a high fistula recurrence rate.

An important step in successful closure of a fistula is accurateidentification and closure of the primary opening. An accurate means ofidentifying the primary opening involves endoscopic visualization of thefistula tract (fistuloscopy), as disclosed in co-pending applicationSer. No. 10/945,634 (Armstrong). Once the primary opening has beenaccurately identified, effective closure is necessary to preventrecurrence. The current invention comprises a graft that may be used toeffectively plug or occlude the primary opening of the fistula tract.

SUMMARY OF THE INVENTION

One object of the present invention is to provide a new technique ofminimally invasive fistula closure. Another object is to provide atechnique that obviates the need for surgical fistulotomy and avoidssurgical pain and the attendant complications of the procedure. Stillanother object of the invention is to provide an accurate and completeclosure of a fistula, thereby preventing a recurrent or persistentfistula. Yet another object of the present invention is to provide atechnique that involves no cutting of tissue, sphincter damage, orincontinence.

The present invention may be used in any type of fistula. For example,the claimed devices and methods may be used to plug or occludetracheo-esophageal fistulae, gastro-cutaneous fistulae, anorectalfistulae, fistulae occurring between the vagina and the urethra orbladder, or fistulae occurring between any other two portions of thebody.

In one embodiment of the present invention, a biocompatible graft havinga curved, generally conical shape is provided. The graft may be used toplug, or occlude the primary opening of the fistula. Desirably, thegraft is approximately 5 to 10 centimeters (2 to 4 inches) long andtapers continuously from a thicker, “trumpet-like” head to a thinfilamentous tail. Desirably, the diameter of the head is approximately 5to 10 millimeters and tapers to a diameter of 1 to 2 millimeters at itstail.

The graft of the present invention may be made of any suitablebiological or synthetic materials. Desirably, the head and the tail areone continuous piece made of the same material. Suitable biologicalmaterials include, but are not limited to, cadaveric allografts fromhuman donors or heterografts from animal tissues. Suitable syntheticmaterials include, but are not limited to, polygalactin, polydioxanoneand polyglycolic acid. Desirably, the biological and/or syntheticmaterial used in the graft of the present invention elicits littleimmunological reaction, has some inherent resistance to infection, andpromotes tissue reconstruction (rather than complete absorption of thegraft into the surrounding tissue), thereby occluding the fistula.

The graft of the present invention may be pulled into the fistula, tailfirst, through the primary opening, toward the secondary opening. In oneembodiment, the graft is drawn into the fistula and the trumpet-likehead end of the graft is gradually “wedged” into the primary opening ina manner similar to that of inserting a plug in a hole. The head and/ortail may be further secured by sutures or other suitable means, whichmay be formed as an integral part of the graft. A trumpet-like headallows the graft to be used for any diameter of primary opening. Byapplying adequate force to the graft during its insertion, the head ofthe graft fits snugly into the primary opening and conforms to the sizeof the primary opening. Multiple or composite grafts may be used formultiple or complex fistulae.

Additional features and advantages of the present invention will beapparent to one of ordinary skill in the art from the drawings anddetailed description of the preferred embodiments below.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows several possible anatomic courses taken by various forms ofanorectal fistula (longitudinal plane);

FIG. 2 shows a perineal view of a simple anorectal fistula and ahorseshoe fistula; and

FIG. 3 shows one embodiment of the graft of the present invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

The graft of the present invention may be used to plug or occlude anytype of fistula, such as the types of fistula illustrated in FIGS. 1 and2. Other types of fistula that may be occluded by the present inventioninclude, but are not limited to, tracheo-esophageal fistulae,gastro-cutaneous fistulae, or fistulae occurring between the vagina andbladder (vesico-vaginal fistulae), between the vagina and urethra(urethro-vaginal fistulae), between the anorectum and vagina(recto-vaginal fistulae), between the anorectum and bladder(recto-vesical fistulae), between the anorectum and urethra(recto-urethral fistulae), between the anorectum and prostate(recto-prostatic fistulae) or between any other two portions of thebody.

The graft 13 of the present invention may have any suitableconfiguration. For example, the graft may have a convex configuration, aconcave configuration, an S-shaped configuration, a generally straightconfiguration, or any other configuration capable of being inserted intoand secured within a fistula. The graft may be curved to conform to theshape of the fistula, thereby facilitating introduction of the graft, asecure fit of the graft within the fistula, and less discomfort for thepatient. A curved configuration makes it easier for the graft to beintroduced into the primary opening and directed toward the secondaryopening of a curved fistula. Desirably, the graft 13 is an integral unitwith a curved, generally conical configuration that tapers from one endhaving a first diameter D1 to an opposite end having a second diameterD2, where the first diameter D1 is greater than the second diameter D2,as shown in FIG. 3.

The graft 13 may have one end with a thicker trumpet-like head 14 and abody 16 that continuously tapers to a thin filamentous tail 15, as shownin FIG. 3. The degree of taper may vary depending on a number offactors, including but not limited to, the diameter of each of the ends(D1 and D2) and the length L of the graft 13.

Although the graft may have any suitable length L, diameter D1, anddiameter D2, desirably, the graft 13 has a length L of about 1 to about15 centimeters, a first diameter D1 of about 1 to about 20 millimeters,and a second diameter D2 of about 0.1 to about 5 millimeters. Moredesirably, the graft 13 has a length L of about 3 to about 12centimeters, a first diameter D1 of about 2 to about 15 millimeters, anda second diameter D2 of about 0.5 to about 3.5 millimeters. Even moredesirably, the graft has a length L of about 5 to about 10 centimeters,a first diameter D1 of about 5 to about 10 millimeters, and a seconddiameter D2 of about 1 to about 2 millimeters. The graft of the presentinvention may be used to close any diameter of primary opening up to thelimits of the head diameter D1. By applying adequate force to the graftduring insertion, the head 14 of the graft 13 conforms exactly to thesize of the primary opening.

The graft 13 of the present invention may be made of any biocompatiblematerial suitable for implantation into a mammalian body. Desirably, thegraft 13 is made of a single, non-allergenic biological or syntheticmaterial.

Suitable biological materials that may be used in the present inventioninclude, but are not limited to, tissue from the patient themselves (anautograft), tissue from a human cadaveric donor (an allograft), ortissue from an unrelated animal donor (a heterograft). Desirably, thematerial promotes angiogenesis and/or site-specific tissue remodeling.

Autograft tissue is grown from a skin biopsy of the patient. Once thefibroblasts have regenerated and formed enough new tissue, the newtissue may be injected back into the surgical site of the same patient.This process takes several weeks to complete, but avoids tissuerejection and disease transmission. One such product is Isolagen(Isolagen Inc.—Houston, Tex.).

Suitable cadaveric materials include, but are not limited to, cadavericfascia and cadaveric dura matar. Specific suitable cadaveric allograftsinclude, but are not limited to, AlloDerm, (LifeCell Corp.—Branchburg,N.J.), Cymetra, (LifeCell Corp.—Branchburg, N.J.), Dermaloga, Fascion(Fascia Biosystems, LLC—Beverly Hills, Calif.), and Suspend(Mentor—Irving, Tex.). These products are freeze-dried, or lyophilized,acellular dermal tissue from cadaveric donors. Some requirereconstitution before implantation. Although disease transmission orantigenic reaction is possible, the risk may be minimized by anextensive screening and processing of the material.

Heterograft materials are taken from a donor of one species and graftedinto a recipient of another species. Examples of such materials include,but are not limited to, Surgisis (Cook Surgical—Bloomington, Ind.),Permacol (TSL—Covington, Ga.), Pelvicol (Bard Inc.—Murray Hill, N.J.)and Peri-Guard, (Bio-Vascular Inc.—St Paul, Minn.). In one embodiment ofthe present invention, an injectable heterograft, such as a heterograftof small intestinal submucosa or other material having a viscositysufficient to prevent the material from running out or being squeezedout of the fistula, is used.

Such biological materials may be rendered non-cellular during processingto avoid immunological rejection. Suitable biological tissues may beimplanted in potentially infected surgical fields and resist infection,unlike some synthetic preparations that may elicit a foreign bodyreaction or act as a nidus for infection.

Desirably, a bioremodelable material is used in the devices and methodsof the present invention. More desirably, a bioremodelable collagenousmaterial is used. Bioremodelable collagenous materials can be provided,for example, by collagenous materials isolated from a suitable tissuesource from a warm-blooded vertebrate, and especially a mammal. Suchisolated collagenous material can be processed so as to havebioremodelable properties and promote cellular invasion and ingrowth andeventual reconstruction of the host tissue itself. Bioremodelablematerials may be used in this context to promote cellular growth withinthe site in which a medical device of the invention is implanted.

Suitable bioremodelable materials can be provided by collagenousextracellular matrix materials (ECMs) possessing biotropic properties.Illustrative suitable extracellular matrix materials for use in theinvention include, for instance, submucosa (including for example smallintestinal submucosa, stomach submucosa, urinary bladder submucosa, oruterine submucosa, each of these isolated from juvenile or adultanimals), renal capsule membrane, dermal collagen, amnion, dura mater,pericardium, serosa, peritoneum or basement membrane materials,including liver basement membrane or epithelial basement membranematerials. These materials may be isolated and used as intact naturalforms (e.g. as sheets), or reconstituted collagen layers includingcollagen derived from these materials and/or other collagenous materialsmay be used. For additional information as to submucosa materials usefulin the present invention, and their isolation and treatment, referencecan be made to U.S. Pat. Nos. 4,902,508, 5,554,389, 5,733,337,5,993,844, 6,206,931, 6,099,567, and 6,331,319. Renal capsule membranecan also be obtained from warm-blooded vertebrates, as described moreparticularly in International Patent Application serial No.PCT/US02/20499 filed Jun. 28, 2002, published Jan. 9, 2003 asWO03002165.

As prepared and used, the ECM and any other collagenous material used,may optionally retain growth factors or other bioactive componentsnative to the source tissue. For example, submucosa or other ECMs mayinclude one or more growth factors such as basic fibroblast growthfactor (FGF-2), transforming growth factor beta (TGF-beta), epidermalgrowth factor (EGF), and/or platelet derived growth factor (PDGF). Aswell, submucosa or other ECM when used in the invention may includeother biological materials such as heparin, heparin sulfate, hyaluronicacid, fibronectin and the like. Thus, generally speaking, the submucosaor other ECM material may include a bioactive component that induces,directly or indirectly, a cellular response such as a change in cellmorphology, proliferation, growth, protein or gene expression.

Further, in addition or as an alternative to the inclusion of suchnative bioactive components, non-native bioactive components such asthose synthetically produced by recombinant technology or other methods,may be incorporated into the material used for the covering. Thesenon-native bioactive components may be naturally-derived orrecombinantly produced proteins that correspond to those nativelyoccurring in an ECM tissue, but perhaps of a different species (e.g.human proteins applied to collagenous ECMs from other animals, such aspigs). The non-native bioactive components may also be drug substances.For example, one drug substance that may be incorporated into and/oronto the covering materials is an antibiotic.

Submucosa or other ECM tissue used in the invention is preferably highlypurified, for example, as described in U.S. Pat. No. 6,206,931 to Cooket al. Thus, preferred ECM material will exhibit an endotoxin level ofless than about 12 endotoxin units (EU) per gram, more preferably lessthan about 5 EU per gram, and most preferably less than about 1 EU pergram. As additional preferences, the submucosa or other ECM material mayhave a bioburden of less than about 1 colony forming units (CFU) pergram, more preferably less than about 0.5 CFU per gram. Fungus levelsare desirably similarly low, for example less than about 1 CFU per gram,more preferably less than about 0.5 CFU per gram. Nucleic acid levelsare preferably less than about 5 μg/mg, more preferably less than about2 μg/mg, and virus levels are preferably less than about 50 plaqueforming units (PFU) per gram, more preferably less than about 5 PFU pergram. These and additional properties of submucosa or other ECM tissuetaught in U.S. Pat. No. 6,206,931 may be characteristic of any ECMtissue used in the present invention.

Suitable synthetic materials that may be used in the present inventioninclude, but are not limited to, polygalactin, polydioxanone, hyaluronicacid, polyglycolic acid, and polyethylene terephthalate. These materialsavoid foreign body rejection and may be eventually incorporated into thehost tissue.

Desirably, the biological or synthetic material used in the presentinvention assists in reconstruction of the host tissues, elicits littleimmunological reaction, and has some inherent resistance to infection.Such material allows incorporation of the graft into the fistula (ratherthan complete absorption of the graft into the surrounding tissue),thereby occluding the fistula.

In one embodiment of the present invention, a drug, such as anantibiotic, is incorporated into the graft of the present invention, asan extra precaution or means of treating any residual infection withinthe fistula. The graft may also be used in conjunction with a sealant orsclerosing solution which may be injected into the main fistula tractand any side branches. Several possible sealants are described in theprior art. One of the more commonly used sealants is fibrin glue, knownas Tisseal (Baxter Inc.). The glue is prepared by mixing coagulationactivation factors with fibrinogen, which react to form fibrin. Thefibrin forms a matrix, which acts as a scaffold for tissue ingrowth andresults in the sealing of the fistula tract.

The graft 13 of the present invention may be inserted into the fistulaby pulling the tail 15 of the graft 13 through the primary opening 2 ofthe fistula and towards the secondary opening 3. This may beaccomplished by using, for example, a pair of surgical hemostats or afistula probe or scope, which is passed through the secondary opening 3and out through the primary opening 2. The tail 15 of the graft 13 maythen be grasped by the hemostats, or secured to the probe or scope, andwithdrawn retrograde into the fistula. As the graft 13 is beingwithdrawn through the fistula, the head 14 of the graft 13 may begradually “wedged” into the primary opening 2 causing the graft 13 tobecome lodged in place so that it does not fall out or exude, as withthe fibrin glue technique.

To assist in anchoring the graft within the fistula, the outer surfaceof the graft may contain protrusions 18 that interact with the fistula.Anorectal fistulae pass through the cylindrical, well-defined internalsphincter muscle 6 containing an almost rigid hole, which is thenarrowest point along the fistula tract. Desirably, the protrusions onthe graft are adapted to be pulled through the hole and wedged againstthe distal portion of the hole to further anchor the graft.

In an alternative embodiment of the present invention, either end of thegraft or both ends of the graft are secured by sutures and trimmed toavoid either end from protruding excessively from the fistula tractafter the procedure. The suture may be formed as an integral part of thegraft or as a separate component.

In another embodiment, the graft is anchored within the fistula bythreading a securing device having a central lumen, over the tail of thegraft and securing it into position at skin level (e.g., by crimpingit). In yet another embodiment, further anchoring of the graft isachieved by using a material such as a small intestinal submucosaheterograft (a freeze-dried material that requires rehydration beforeuse) for the graft and inserting the graft into the tract before thegraft material has been fully expanded by hydration. Any other suitablemeans of securement, such as introducing adhesive into the fistulatract, may also be used to anchor the graft within the fistula.

In one embodiment, antologous fibrin glue is used in conjunction withthe fistula graft to supplement the adhesive and occlusive properties ofthe disclosed invention. This involves the use of an autologouscomposite of platelets and growth factors derived from the patient's ownblood. (Symphony PCS, DePuy AcroMed Inc.). The composite may be derivedfrom a fresh sample of blood drawn from the patient at the time ofsurgery. The blood may then be centrifuged, and the platelets, whichcontain growth factors such as epidermal growth factor (EGF) andtransforming growth factor—beta (TGFβ), harvested. Having centrifugedthe blood, retrieved the platelet “pellet” and prepared the composite,the sealant may then be injected into the fistula tract(s) to helpmaintain the graft in place.

Closure of a fistula tract may be performed as a one-stage or two-stageprocedure. As a one-stage procedure, the fistula tract is closed orsealed at the same time as the initial surgery. The advantage of thismethod is that it avoids a second operation and minimizes expense andinconvenience. The main disadvantage is that immediate implantation ofthe graft into an “unprepared” and possibly infected fistula tract mayresult in secondary infection of the graft. As a two-stage procedure, aseton is first placed through the fistula tract to allow mechanicaldrainage of the fistula tract. Several weeks later, the seton is removedand the graft is inserted into the fistula.

An alternative methodology involves preliminary endoscopic visualization(fistuloscopy) and “cleaning” of the fistula tract, as disclosed inco-pending application Ser. No. 10/945,634 (Armstrong). This proceduremay be performed by a very thin flexible endoscope, which is insertedinto the secondary opening of the fistula tract, and advanced underdirect vision through the fistula tract and out the primary opening. Byperforming preliminary fistuloscopy of the fistula tracts, the primaryopening is accurately identified and the tracts are “cleaned out” bymeans of an irrigating fluid. Any inflammatory or necrotic tissue withinthe tract is therefore removed, prior to inserting the graft. The tailof the graft may be attached to the fistuloscope, which may then bewithdrawn through the fistula tract so that the graft gets wedged inplace, as described above.

For multiple fistula, multiple grafts may be inserted until all fistulatracts have been closed. In the case of a complex fistula, for instancethe horseshoe fistula, there may be one primary opening and two or moretracts leading from that opening. In this instance, a graft may beconfigured with one “head” component (larger diameter end), and two“tails” (smaller diameter ends). Desirably, accurate identification ofall fistula tracts and the primary opening is facilitated by firstperforming fistuloscopy. Once the entire tract has been identified andcleaned out, each tail may be pulled through the primary opening intoeach fistula in turn, desirably using a fistuloscope or an instrumentpassed through the instrument channel of a scope. Adequate force may beapplied to the tail to ensure that the head of the graft is firmlysecured in the primary opening. The head of the graft and/or each of thetails may be further secured by any of the methods described above.

The success of the present invention was demonstrated in a clinicaltrial evaluating the efficacy of a biodegradable lyophilized porcinesubmucosa plug, as compared to the fibrin glue technique, in closinganorectal fistulae. Thirteen of fifteen patents (87%) treated with theplug had complete closure of all fistula tracts, whereas only four often (40%) patents treated with the fibrin glue technique had completeclosure.

It is intended that the foregoing detailed description be regarded asillustrative rather than limiting, and that it be understood that it isthe following claims, including all equivalents, that are intended todefine the spirit and scope of this invention.

The invention claimed is:
 1. A method of treating a fistula of a humanpatient, the fistula having a tract extending from a first opening in afirst body lumen to a second opening, the method comprising inserting aplug into the first opening of the tract so as to occlude said firstopening, wherein the plug comprises non-cellular bioremodelable materialthat promotes cellular invasion and ingrowth and reconstruction of hosttissue within the plug, and wherein the bioremodelable material isselected from the group consisting of a cadaveric material from a humandonor and a heterograft material from a non-human donor, and positioningthe plug in the tract whereby the bioremodelable material extends alongthe fistula tract from the first opening to the second opening andpromotes cellular invasion and ingrowth and reconstruction of hosttissue within the plug, wherein the second opening is an opening in asecond body lumen or on an exterior surface of the patient.
 2. Themethod of claim 1, wherein the fistula is selected from the groupconsisting of: a tracheo-esophageal fistula, a gastro-cutaneous fistula,an anorectal fistula, a recto-vaginal fistula, a recto-vesical fistula,a recto-urethral fistula, a recto-prostatic fistula, a vesico-vaginalfistula and an urethro-vaginal fistula.
 3. The method of claim 1,wherein the bioremodelable material is a collagenous extracellularmatrix material.
 4. The method of claim 1, wherein the bioremodelablematerial is selected from the group consisting of submucosa, smallintestinal submucosa, stomach submucosa, urinary bladder submucosa,uterine submucosa, renal capsule membrane, dermal collagen, amnion, duramater, pericardium, serosa, peritoneum, basement membrane, liverbasement membrane and epithelial basement membrane.
 5. The method ofclaim 1, wherein the bioremodelable material is an intact acellularsheet of a collagenous extracellular matrix material.
 6. The method ofclaim 1, wherein the bioremodelable material is dermal collagen.
 7. Themethod of claim 1, wherein the bioremodelable material is submucosa. 8.The method of claim 7, wherein the submucosa is small intestinalsubmucosa.
 9. The method of claim 1, wherein the bioremodelable materialcomprises an intact acellular sheet of dermal collagen or submucosa. 10.The method of claim 1, wherein the plug further comprises a non-nativebioactive.
 11. The method of claim 10, wherein the non-native bioactiveand the bioremodelable material are derived from different species. 12.The method of claim 1, further comprising securing the plug to tissue ofthe patient adjacent to at least one of the first opening and the secondopening.
 13. The method of claim 12, wherein the securing the plug totissue of the patient comprises suturing the plug to tissue of thepatient.
 14. The method of claim 1, further comprising applying amaterial selected from the group consisting of an adhesive and fibringlue to the fistula track.
 15. The method of claim 1, wherein the plugcomprises a head and a tail, wherein the tail is thinner than the head.16. A method of treating a fistula of a human patient, the fistulahaving a tract extending from a first opening to a second opening, themethod comprising inserting a plug into the first opening of the tractso as to occlude said first opening, wherein the plug comprisesnon-cellular bioremodelable material that promotes cellular invasion andingrowth and reconstruction of host tissue within the plug, and whereinthe bioremodelable material is selected from the group consisting ofdermal collagen and submucosa, and positioning the plug in the tractwhereby the bioremodelable material extends along the fistula tract fromthe first opening to the second opening and promotes cellular invasionand ingrowth and reconstruction of host tissue within the plug, whereinthe first opening is an opening is an opening in a first body lumen thesecond opening is an opening in a second body lumen or on an exteriorsurface of the patient.
 17. The method of claim 16, wherein the plugincorporates a non-native bioactive.
 18. A method of treating a fistulaof a human patient, the fistula having a tract extending from a firstopening to a second opening, the method comprising inserting a plug intothe first opening of the tract so as to occlude said first opening,wherein the plug comprises non-cellular bioremodelable material and anon-native bioactive, and wherein the bioremodelable material comprisesa collagenous extracellular matrix material, and positioning the plug inthe tract whereby the bioremodelable material extends along the fistulatract from the first opening to the second opening and promotes cellularinvasion and ingrowth and reconstruction of host tissue within the plug,wherein the first opening is an opening is an opening in a first bodylumen the second opening is an opening in a second body lumen or on anexterior surface of the patient.
 19. The method of claim 18, wherein thefistula is selected from the group consisting of: a tracheo-esophagealfistula, a gastro-cutaneous fistula, an anorectal fistula, arecto-vaginal fistula, a recto-vesical fistula, a recto-urethralfistula, a recto-prostatic fistula, a vesico-vaginal fistula and anurethro-vaginal fistula.